The objectives of this research project are to define the role of the glandular kallikrein-kinin system in normal renal function via effects upon membrane ion transport processes. Studies will be conducted in the various levels including epidemilogical, clinical, pharmacological and biochemical approaches. Efforts will be expanded to the studies of the relations among urinary kallikrein, blood pressure, salt apetite and other variables in normal infants. Studies of glandular kallikrein levels in the urine and serum of diabetic patients and animal models will be continued via application of the new direct radioimmunoassay for human and rat glandular kallikrein. Studies of human urinary pre-kallikrein, an inactive form of glandular kallikrein formed in human urine, will be carried out in normal and pathological states. Work will be carried out on amiloride and amiloride analogue inhibition of purified kallikrein and the relations of this event to the mechanism of action of this drug and to ion transport across appropriate membranes. The effect of kallikrein inhibitors, antibodies and other components of the kallikrein-kinin system upon ion tranport across appropriate membranes will be studied. Studies will be continued on measuring kallikrein levels, production and release in isolated tissues and cells from animals treated with various antihypertensive and diuretic drugs or steroid hormones. Regulation of kallikrein synthesis by drugs and steroid hormones will be studied in isolated cell suspensions and tissue slices.